Circadian variations in the levels of prostaglandins (PGs) D2, E2, and F2 alpha were studied in the cerebrospinal fluid (CSF) of rats. We collected CSF samples from the cisterna magna of anesthetized rats at different clock-hours (1000, 1400, 1800, 2200, 0200, and 0600 hr), and measured the concentrations of the three PGs. PGD2, which appeared to be the most abundant among the three, showed a circadian variation; and the mean of the day-time levels (145 pg/ml) was significantly higher than that of the nighttime ones (111 pg/ml). Day/night variations were also noticed with the levels of PGE2 and PGF2 alpha; however, these levels remained 3-4 times lower than those of PGD2. The general day/night variation seen in the CSF concentration of PGD2 conforms well with the postulated role of PGD2 as an endogenous sleep-promoting factor acting on a certain brain surface area defined as its site of action.